Feedlot heart disease: understanding heart score and its relationships to economically relevant traits

Includes bibliographical references.2022 Fall.The increasing occurrence of feedlot heart disease caused by pulmonary hypertension has precipitated a growing concern from producers and geneticists alike. Utilization of genetic technology for selection and breeding decisions has made a substantial amount of progress in past decades within economically relevant traits, but the focus on high performing cattle may have had adverse consequences on cardiovascular fitness. Pulmonary hypertension has become a more frequent occurrence in low to moderate elevation feedlots, causing feedlot death and the potential to predispose cattle to co-morbidities. Previously, once considered only a high-altitude issue, pulmonary hypertension appears prevalent in high genetic merit cattle within moderate elevation, high plains feedlots. With no options for treatment, management, and prevention in feedlot cattle may be the only strategy for producers struggling with the balance of desirable, fattening cattle and pulmonary hypertension risk. The objective of this study was to establish the foundation for a new heart grading system known as heart score and discover its genetic and phenotypic relationships with economically relevant traits and differentiate phenotypic differences between healthy and unhealthy scored Angus-influenced cattle. The third chapter of this thesis included phenotypic differences between cattle with healthy and unhealthy heart scores (n = 1,422). Data were obtained from Cactus Feed Yard LLC in Canyon, Texas over a two-year period (2020-2022). Means were compared between heart score groups (1,2 & 3+) to test for significant differences between the two groups. Linear models and the ANOVA table displayed significant fixed effects to each model. Systolic, diastolic, PAP, and marbling scores differed among groups (P < 0.05), while hot carcass weight displayed a tendency (P < 0.10). Unhealthy heart scored cattle tended to be heavier carcasses associating heavier cattle with pulmonary hypertension. Healthy heart scored animals had overall lower (P < 0.05 ) PAP, systolic, and diastolic measurements. The fourth chapter of this thesis highlighted the differences between repeated PAP measurements at 9 and 14 months of age. The cohort of Angus influenced cattle were housed at a feedlot in Canyon, TX and was a moderate altitude (1,080 m). Repeated PAP measurements exhibited an increase in PAP measurements between 9 months and 14 months of age, which were later grouped by their heart scores. No differences were observed among heart scored cattle at 9 months (mean minimum: 39.61 ± 2.47; mean maximum: 40.36 ± 3.47) but distinct differences were observed among cattle grouped in their 14-month PAP (mean minimum: 45.27 ± 5.69; mean maximum: 79.20 ± 21.09). High heart scores were associated with higher PAP measurements. There was a correlation of 0.20 between the measurements showcasing a positive trend between measurements, but also the inability of PAP measurements taken at 9 months may not be predictive of cattle's scores at 14-month-old. Furthermore, there were no differences between phenotypic traits of the cattle who had greater PAP differences between their measurements. The third study estimated the heritability of heart score and the phenotypic relationships with economically relevant traits (n = 1,507) in progeny of 88 sires. Phenotypes included heart scores, PAP (14 months), hot carcass weight, marbling, ribeye area, and backfat. Heart score was found to have a moderate heritability estimate 0.28 ± 0.10. Heart score had a very strong genetic correlation with PAP, and strong correlation with hot carcass weight. Positive genetic correlations were found between heart scores and carcass traits with genetic correlations between 0.07 to 0.63. Overall, these results suggest heart scores to be useful in genetic selection for a healthier cardiopulmonary system. while not drastically influencing carcass traits

Masters of Science in Environmental Science and Policy Portfolio

Through my work as a Master’s student in Environmental Science and Policy at Clark University I have acquired a wide variety of knowledge and skills which will be showcased in this document. The breadth of courses and sub disciplines that I have taken has expanded my awareness and understanding of the current state of Environmental Science and Policy. My undergraduate degree from Clark University in Environmental Science focusing on Earth Systems Science focused primarily on comprehension of the Earth’s physical processes with applications for Global Climate Change. This master’s work has expanded upon those quantitative skills as well as deepened my understanding of American environmental legislation and has encouraged creative solutions in building a sustainable future. This portfolio is meant to represent the variety of knowledge that I have acquired through my work at Clark University’s Environmental Science and Policy program including the state of climate denial in America, analyses of municipal environmental policies, social practices and their climate impacts, quantitative analyses of climate data, and critical examinations of energy systems. Some of the work showcased in the following pages was collaborative in nature as many courses in this program aim to simulate the collaborative nature of the field and the increasing collaborative nature of our world. In order to promote a sustainable future within the capitalist framework that we live in, we must look at what it means to sustainably consume and produce. Through my work at Clark, particularly in a course called Sustainable Consumption and Production, I examined the structure of hyper consumerism, the concepts of well-being in America as it pertains to sustainability, growth within the capitalist framework, and the usefulness and downsides of technical 3 efficiencies to promote sustainability. The first paper included in this portfolio was a group endeavor that examined New York City’s extensive OneNYC Plan for a Strong and Just City. This paper summarizes the extensive plan put out by the Mayor’s Office and analyzes the plan based on how the concepts of human well-being, consumptive behavior and growth of the economy play into the sustainability of the city. The second paper is a quantitative research project done using statistical analyses to compare historical O18 isotope ratios from coral cores at variety of locations around the globe. These ratios tend to be highly correlated with water temperatures. The analysis of historical coral cores is a technique used to give us a clearer idea of the paleoclimate. The raw data for this project was acquired from the National Oceanic and Atmospheric Administration’s (NOAA) National Climatic Data Center (NCDC). This project is one of the many exercises at Clark that tailored my ability to obtain, clean and organize data from external sources. In a time where we are well on our way to reaching dangerously high levels of Green House Gasses in our atmosphere, I am committed to working towards a more sustainable future for ourselves and for future generations. Unfortunately, an alarming large percentage of the American population does not support the idea that climate change is a human induced phenomenon. The third paper here addresses climate denial in America and analyses and refutes arguments that are commonly used. My team and I examined the demographics of the communities that are most likely to deny human induced climate change, the actual arguments leaders of this movement tend to use, and, most importantly, examined techniques that can be harnessed to discuss climate change with those who do not believe in it. Communication with those who do not understand or agree with the grave implications involved with human induced climate change is vital to promoting a sustainable future. 4 The fourth paper is a discussion on the solar photovoltaic market which accompanies a solar panel planning spread sheet that I created to help companies or individual consumers can forecast their expenses and potential revenue from installing a single solar panel or a solar array. This paper discusses the historical increase in efficiencies of solar photovoltaics and the innovation that has occurred as well as the steep decrease in cost of photovoltaics since their release on the market in the 1970’s. Overall, this portfolio represents a wide variety of knowledge and skills that I have acquired through my Master’s education at Clark University. Each piece of work, carefully chosen to be included here, represents a larger body of knowledge and experiences that I have acquired through my time at Clark University. Clark’s Environmental Science and Policy program has helped cultivate me to be thoughtfully critical of environmental policies through collaborative and individual work. It has provided scientific training in environmental decision making and has fueled my commitment to finding creative solutions to promote a sustainable future and culture

Structural characterization of febuxostat and its impurities by HPLC-DAD-MSn method

Giht je metabolička bolest karakterizirana ponavljanim napadima upalnog artritisa čiji je glavni uzrok stanje povećane koncentracije mokraćne kiseline u krvi, hiperuricemija. Srećom, postotak je populacije s dijagnozom gihta još uvijek nizak, međutim, incidencija je gihta u porastu. Ukoliko bolest nije dobro kontrolirana nefarmakološkim mjerama, potrebna je administracija lijekova, pri čemu glavnu ulogu imaju lijekovi za snižavanje razine mokraćne kiseline u krvi. Prva je linija liječenja alopurinol, ali, u slučaju neučinkovitosti ili nepodnošenja alopurinola, lijek je izbora febuksostat. Febuksostat je relativno nov lijek – selektivan, nepurinski inhibitor ksantin oksidaze, enzima koji katalizira nastajanje mokraćne kiseline u organizmu. Učinkovit je u prevenciji i smanjenju učestalosti akutnih napada gihta. Febuksostat još uvijek nema svoju monografiju u Europskoj farmakopeji, stoga je potrebno razviti brze, selektivne, osjetljive i točne metode za potvrdu identiteta, ispitivanje čistoće te određivanje sadržaja febuksostata u aktivnim farmaceutskim supstancijama i gotovim ljekovitim oblicima. Cilj je ovog diplomskog rada ispitivanje čistoće febuksostata. Korištena je visoko sofisticirana HPLC-DAD-MSn metoda te je postignuto odjeljivanje febuksostata i njegovih triju onečišćenja (febuksostat amid, febuksostat DEE, etil-febuksostat), a nakon toga masenom su spektrometrijom pretpostavljeni fragmentacijski putovi svakog analita. Predloženi fragmentacijski putovi mogu pomoći u razumijevanju profila onečišćenja febuksostata te olakšati i ubrzati ispitivanje njegove čistoće u gotovom ljekovitom obliku. S tim je ciljem pripremljen i analiziran uzorak febuksostata ekstrahiranog iz tablete, a uočeno je više kromatografskih pikova koji odgovaraju onečišćenjima. Od triju interesnih onečišćenja, u uzorku febuksostata iz tablete detektirana su dva, dok se prisutnost trećeg onečišćenja ne može sa sigurnošću potvrditi. Također, uočena su još četiri pika onečišćenja koje u nastavku rada treba strukturno karakterizirati i identificirati.Gout is a metabolic disease characterized by recurrent attacks of inflammatory arthritis. It is mostly connected with the state of abnormally high blood level of uric acid called hyperuricemia, which is considered to be the main cause of gout. The percentage of the population diagnosed with this disease is quite small, but the incidence of gout tends to grow nowadays. If non-pharmacological measures are not effective in controlling the disease, drug administration is needed. Although there are a few pharmacological groups of drugs that can be used in gout treatment, the main role is played by drugs that lower the blood concentration of uric acid. Allopurinol represents the first line of treatment, but in the case of its ineffectiveness or intolerance, febuxostat can be used. Febuxostat is a relatively new drug, which acts like selective, non-purine xanthine oxidase inhibitor. Xanthine oxidase is an enzyme that catalyzes the production of uric acid, therefore, its inhibition may help prevent and reduce the frequency of acute gout attacks. Febuxostat still does not have an official monograph in pharmacopoeia so it is highly necessary to develop fast, selective, sensitive and accurate analytical methods for the identification and determination of febuxostat and its impurities in active pharmaceutical ingredients and finished drug products. The aim of this diploma thesis was to analyze impurities in febuxostat. In order do to so, highly sophisticated HPLC-DAD-MSn method was used to separate febuxostat and its three impurities (febuxostat amide, febuxostat DEE, ethyl-febuxostat). Then, fragmentation pathways for all analytes were determined using mass spectrometry. Suggested pathways of fragmentation can be helpful in understanding the impurity profile of febuxostat, and can also contribute to a fast and easy way of impurity profiling of finished drug product. Hence, the sample of febuxostat extracted from a tablet was taken and analyzed. Many chromatographic peaks that matched impurities were noticed. Two out of three impurities of interest were detected in this sample, while the presence of the third impurity could not be confirmed with certainty. Also, four more peaks were noticed but they will be structuraly characterized and identified in later research

Tetrahidrobiopterin koncentráció stabilizálása és nitrogén oxid szintézis optimalizálása aszkorbáttal és tiol vegyületekkel normális és preeclampsiás terhesek placentájában = Stabilization of tetrahidrobiopterin concentration and optimization of nitric oxide synthesis by ascorbate and thiol compounds in placentae of normal and preeclamptic pregnancies

Kísérleteinkben azt vizsgáltuk meg, hogy aszkorbát (ASC) és glutation (G-SH) milyen szerepet játszhatnak (1) az NO szintázok (NOS) tetrahidrobiopterin koenzimének (BH4) stabilizálásában, (2) az NO felszabadításában nitrozótiolokból illetve glicerintrinitrátból (GTN) és (3) a normális perfúzió fenntartásában egészséges és kóros placentákban. A BH4 autooxidáció miatt gyorsan inaktiválódik. Kimutattuk, hogy mind ASC mind GSH koncentráció-függő módon gátolja a BH4 autooxidációját. Az ASC gátlás (szemben a GSH gátlással) nem hőmérsékletfüggő. Az ASC hatás mechanizmusa a •BH3 gyök gyors visszaredukálása BH4-é. A GSH támadáspontja elsősorban a qBH2 (kinoidális BH2) átalakítása BH4-é. Az ASC és a GSH eltérő hatásmechanizmusát megerősítette a két vegyület protektív hatásának additivitása. Terhesség-indukálta hipertóniában a placenta ASC és tiol tartalmának csökkenését találtuk. Az NO kémiai felszabadításának egy további lehetőségeként megfigyeltük, hogy ASC mobilizálja az NO-t stabil nitzozótiolokból, így nitrozóglutationból (GSNO). Spektrális vizsgálataink egyértelműen bizonyították, hogy ASC GTN-ből vagy nitritből vagy GSNO-ból, akár oxihemoglobin akár methemoglobin jelenlétében NO-t tesz szabaddá. A hatásmechanizmusban fontos a deoxihemoglobin képződése és ciklusos újraképződése ASC és kataláz jelenlétében. A GTN-ből, nitritből és GSNO-ból ASC illetve ditionit jelenlétében, hemoglobin hatására történő NO képződés mechanizmusának számos részletét feltártuk. | The aim of our experiments was to clarify the roles of ascorbate (ASC) and glutathione (GSH) (I) in the stabilization of tetrahydrobiopterin coenzyme (BH4) of NOS, (II) in the release of NO from nitrosothiols and glyceryltrinitrate (GTN) and (III) in the maintenance of normal placental perfusion. The results indicated a concentration dependent inhibition of BH4 autooxidation both by ASC and GSH. Inhibition by ASC (but not by GSH) was independent from temperature . The mechanism of ASC action is a rapid reduction of •BH3 radical back to BH4. GSH seems to promote primarily the reduction of qBH2 (quinoidal BH2) to BH4. The differential mechanism of action of ASC and GSH was confirmed by demonstrating their additive effect. In cases of pregnancy-induced hypertension we observed decreases of ASC and thiol contents of the placenta. As a further possibility for chemical liberation of NO, we found that ASC can mobilize NO from stable nitrosothiols, including nitrosoglutathione (GSNO). We provided evidence that ASC is able to release NO from GTN or nitrite or GSNO in the presence of either oxyhemoglobin or methemoglobin. A unique feature of the mechanism of this ASC effect is the formation and cyclic renewal of deoxyhemoglobin in the presence of catalase. In addition, our experiments elucidated numerous details of hemoglobin-stimulated NO formation in response to ASC or dithionite, from GTN, nitrite and NO-thiols, respectively

Quantitative structure–activity relationship (QSAR) analysis of aromatic effector specificity in NtrC-like transcriptional activators from aromatic oxidizing bacteria

A quantitative structure–activity relationship (QSAR) approach was taken to provide mechanistic insights into the interaction between the chemical structure of inducing compounds and the transcriptional activation of aromatic monooxygenase operons among the XylR/DmpR subclass of bacterial NtrC-like transcriptional regulators. Compared to XylR and DmpR, a broader spectrum of effector compounds was observed for the TbuT system from Ralstonia pickettii PKO1. The results of QSAR analysis for TbuT suggested that a steric effect, rather than hydrophobic or electronic effects, may be the predominant factor in determining aromatic effector specificity, and the active site of the regulator may positively interact not only with the methyl moiety but also with the most electron-rich aryl side of an aromatic effector.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74885/1/S0378-1097_03_00400-2.pd